Human immunodeficiency virus infection and related diseases are a major public health problem worldwide. Human immunodeficiency virus type 1 (HIV-1) encodes three enzymes which are required for viral replication: reverse transcriptase, protease, and integrase. Although drugs targeting reverse transcriptase and protease are in wide use and have shown effectiveness, particularly when employed in combination, toxicity and development of resistant strains have limited their usefulness (Palella, et al. N. Engl. J Med. (1998) 338:853-860; Richman, D. D. Nature (2001) 410:995-1001).
A goal of antiretroviral therapy is to achieve viral suppression in the HIV infected patient. Treatment guidelines published by the United States Department of Health and Human Services provide that achievement of viral suppression requires the use of combination therapies, i.e., several drugs from at least two or more drug classes. In addition, decisions regarding the treatment of HIV infected patients are complicated when the patient requires treatment for other medical conditions. Because the standard of care requires the use of multiple different drugs to suppress HIV, as well as to treat other conditions the patient may be experiencing, the potential for drug interaction is a criterion for selecting a drug regimen. Therefore, there is a need for antiretroviral therapies having a decreased potential for drug interactions.
Despite the success of potent and well-tolerated anti-retroviral therapy (ART), mutations of the HIV-1 virus continue to occur in clinical settings. For example, some treatment-experienced patients on ART experience drug resistance. As a result, achieving virological suppression in this patient population is complex. In view of these challenges, there remains a significant medical need for safe and effective new therapies that address virologic resistance. Moreover, new therapies for patients experiencing virologic resistance must also: (i) exhibit tolerability, long-term safety, and adherence (Costagliola D. Demographics of HIV and aging Curr. Opin. HIV AIDS, 2014, 9(4), 294); as well as (ii) consider the aging patient population, non-HIV-related comorbidities, and regimen simplification.
As discussed in PCT Publication no. WO1995/06030, darunavir demonstrates antiviral activity.
Darunavir (Formula I) has the following structure:

There is a need for stable forms of the compound of Formula I with suitable chemical and physical stability for the formulation, therapeutic use, manufacturing, and storage of the compound.